美国凯斯西储大学医学院Paul J. Tesar小组的一项最新研究发现了瞬时基因融化决定了少突胶质细胞成熟的时间。2025年8月25日，国际知名学术期刊《细胞》发表了这一成果。

课题组报告了一种调控少突胶质细胞成熟时间的转录机制。在祖细胞分化为未成熟的少突胶质细胞后，转录因子SOX6在特定基因体中从超增强子重新分配到细胞。这些位点表现出广泛的染色质去浓缩和转录，在成熟时突然关闭。抑制SOX6使这些不成熟的基因座失活，加速向成熟的髓鞘少突胶质细胞的过渡。值得注意的是，含有这种未成熟SOX6基因标记的细胞在多发性硬化症患者的大脑中富集，反义寡核苷酸介导的SOX6敲低驱动小鼠少突胶质细胞成熟。他们的研究结果证实SOX6是少突胶质细胞成熟的关键调节因子，并强调其作为促进疾病髓鞘形成的治疗靶点的潜力。

研究人员表示，细胞成熟是组织形成和功能的关键步骤，不同于分化和细胞命运规范的初始步骤。在中枢神经系统中，少突胶质细胞成熟失败与多发性硬化症等疾病有关。

附：英文原文

Title: Transient gene melting governs the timing of oligodendrocyte maturation

Author: Kevin C. Allan, Jesse J. Zhan, Andrew R. Morton, Erin F. Cohn, Marissa A. Scavuzzo, Anushka Nikhil, Matthew S. Elitt, Benjamin L.L. Clayton, Lucille R. Hu, H. Elizabeth Shick, Jost K. Vrabic, Hannah E. Olsen, Daniel C. Factor, Jonathan E. Henninger, Gemma Bachmann, Berit E. Powers, Richard A. Young, Charles Y. Lin, Peter C. Scacheri, Tyler E. Miller, Paul J. Tesar

Issue&Volume: 2025-08-25

Abstract: Cellular maturation is a crucial step for tissue formation and function, distinct from the initial steps of differentiation and cell fate specification. In the central nervous system, failure of oligodendrocyte maturation is linked to diseases such as multiple sclerosis. Here, we report a transcriptional mechanism that governs the timing of oligodendrocyte maturation. After progenitor cells differentiate into immature oligodendrocytes, the transcription factor SOX6 redistributes from super-enhancers to cluster across specific gene bodies. These sites exhibit extensive chromatin decondensation and transcription, which abruptly turn off upon maturation. Suppression of SOX6 deactivates these immaturity loci, accelerating the transition to mature, myelinating oligodendrocytes. Notably, cells harboring this immature SOX6 gene signature are enriched in multiple sclerosis patient brains and antisense oligonucleotide-mediated Sox6 knockdown drives oligodendrocyte maturation in mice. Our findings establish SOX6 as a key regulator of oligodendrocyte maturation and highlight its potential as a therapeutic target to promote myelination in disease.

DOI: 10.1016/j.cell.2025.07.039

Source: https://www.cell.com/cell/abstract/S0092-8674(25)00861-X